In this episode, I’ll discuss whether the duration of treatment for pseudomonas VAP can be shortened to 8 days.
For most patients with ventilator associated pneumonia, an 8 day course of therapy is adequate. However, for patients with VAP caused by non-fermenting gram negative bacteria – especially pseudomonas – a longer duration of treatment is necessary to be considered adequate.
A group of authors from Sorbonne University in Paris, France conducted a randomized open label multicenter trial to examine whether an 8 day course of therapy for Pseudomonas VAP (PA-VAP) could be non-inferior to a 15 day course.
186 patients were analyzed for achieving a composite endpoint combining mortality and PA-VAP recurrence rate during hospitalization in the intensive care unit (ICU) within 90 days.
25 of 98 patients in the 15-day group and 31 of 88 patients in the 8-day group reached the composite endpoint. This was 25.5% in the 15-day vs 35.2% in the 8-day group. The authors pre-specified the use of a 90% confidence interval for their analysis, and even though there was a nearly 10% higher endpoint rate in the 8-day group, the 90% confidence interval included zero and therefore non-inferiority was reached. The rates of mechanical ventilation, length of ICU stay, number of extra pulmonary infections and acquisition of multidrug-resistant (MDR) pathogens during ICU stay were similar between groups.
The authors concluded their study showed no differences in the composite or separate outcomes (90-day mortality or VAP recurrence) between short- and long-duration treatments for PA-VAP but acknowledge that it was under powered.
While it is true that the selection of a 95% confidence interval for statistical analysis is arbitrary, and a 90% confidence interval could well be considered clinically relevant, I see no reason to use a weaker measure of non-inferiority for this study compared with the 95% confidence interval that has been traditionally used to compare therapies. And while I appreciate the desire to reduce unnecessary antibiotic use, I don’t think that this study can be used to establish the clinical non-inferiority of a shorter course of antibiotics for the serious condition of Pseudomonas VAP. Until a larger study or a well-constructed meta-analysis show otherwise, it seems prudent to focus stewardship efforts for shortening antibiotic duration on other disease states.
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